This is a proposal to continue a program project with the overall goal of defining molecular and cellular mechanisms of seizures and determining their anatomical correlates. The program consists of seven inter-related, complementary component projects with the following major objectives: 1) To define the roles of cyclic nucleotides and biochemical systems linked to cyclic nucleotide metabolism in CNS in pathophysiologic mechanisms of seizures; 2) to determine the relations of membrane lipids to epilepsy and determine the effects of anticonvulsant drugs on the developing nervous system; 3) to systematically define the role of local neuronal circuits of the basal ganglia in the development, maintenance, termination and functional anatomy of focal motor seizures; 4) to characterize pathophysiological mechanisms involved in the generation and spread of seizures in the limbic system and determine how specific neuroanatomical pathways influence limbic seizures; 5) to define anatomical, biochemical, pathological and pharmacological mechanisms involved in focal seizures; 6) to characterize, electrophysiologically, the human sensorimotor and language cortex for the purpose of improving neurosurgical procedures and to elucidate physiologic mechanisms at both a systems and cellular level that have a special relevance to epilepsy; and 7) to implement the use of positron emission tomography (PET) in the evaluation of patinets with epilepsy. The program brings together several excellent and productive basic and clinical scientists with skills and interests in the fields of anatomy, biochemistry, physiology, pharmacology, radiology and basic and clinical neurosciences. Our research should provide a greatly improved understanding of epilepsy and eventually may improve diagnosis and treatment of patients with this disorder.